Mycothiol regulates and is regulated by a thiol-specific antisigma factor RsrA and σR in Streptomyces coelicolor
Mycothiol regulates and is regulated by a thiol-specific antisigma factor RsrA and σR in Streptomyces coelicolor
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DOI：
10.1111/j.1365-2958.2008.06191.x
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发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Roe, Jung-Hye
中科院分区：
文献类型：
--
作者：
Park, Joo-Hong;Roe, Jung-Hye
真菌硫醇（MSH）是一种小硫醇分子，具有半胱氨酸连接的二糖结构，存在于放线菌（包括链霉菌和分枝杆菌）中。在天蓝色链霉菌（Streptomycescoelicolor）（抗生素生产和分化的模式生物）中，MSH的量受sigma因子sigma（R）的控制，其受具有硫醇-二硫化物氧化还原开关的反sigma因子RsrA调节。我们发现，MSH生物合成途径中的第一个基因（mshA）和参与解毒真菌硫醇反应性药物的酰胺酶（mca）基因都受sigma（R）的直接控制。sigma（R）靶基因不仅由硫醇氧化剂二酰胺诱导，而且由引起MSH快速降低的烷化剂诱导。在MSH缺陷突变体中，sigma（R）调节子的表达也升高，表明MSH水平的降低是sigma（R）激活的天然细胞内触发因素。我们发现MSH能够还原RsrA以结合sigma（R），而谷胱甘肽不能。这些结果支持RsrA-sigma（R）系统感测细胞内水平的还原MSH的提议，并且MSH除了作为氧化还原缓冲液和药物解毒剂之外还作为转录系统的天然调节剂用于其自身的补充。
Mycothiol (MSH) is a small thiol molecule with a cysteine-ligated disaccharide structure found in actinomycetes that include streptomycetes and mycobacteria. In Streptomyces coelicolor, a model organism for antibiotic production and differentiation, the amount of MSH is under the control of a sigma factor sigma(R), which is regulated by an antisigma factor RsrA with a thiol-disulphide redox switch. We found that the first gene (mshA) in the biosynthetic pathway for MSH and the gene for amidase (mca) that participates in detoxifying mycothiol-reactive drugs are under direct control of sigma(R). The sigma(R) target genes are induced not only by a thiol oxidant diamide, but also by alkylating agents that cause a rapid decrease in MSH. Expression of the sigma(R) regulon was also elevated in MSH-deficient mutants, suggesting that a decrease in the level of MSH is a natural intracellular trigger for sigma(R) activation. We found that MSH was capable of reducing RsrA to bind sigma(R), whereas glutathione was not. These results support a proposal that the RsrA-sigma(R) system senses the intracellular level of reduced MSH, and that MSH serves as a natural modulator of the transcription system for its own replenishment in addition to being a redox buffer and drug detoxifier.